Abstract

BACKGROUND:

Limited data from positron emission tomography (PET) studies of subjects with attention-deficit/hyperactivity disorder (ADHD) indicate alterations in brain dopamine neurotransmission. However, these studies have used conventional univariate approaches that are less sensitive to detect complex interactions that may exist between different brain dopamine pathways and individual symptoms of ADHD. We aimed to investigate these potential interactions in adolescents with ADHD.

METHODS:

We used a 3D PET scan to measure utilization of native L-[11C]-DOPA to map dopamine presynaptic function in various cortical, striatal and midbrain regions in a group of 8 male adolescents with ADHD and 6 age matched controls. To evaluate the interactions between the studied brain regions, multivariate statistical methods were used.

RESULTS:

Abnormal dopaminergic function was found in multiple brain regions of patients with ADHD. A main finding was lower L-[11C]-DOPA utilization in adolescent with ADHD as compared to control subjects, especially in subcortical regions. This pattern of dopaminergic activity was correlated specifically with symptoms of inattention.

CONCLUSION:

Dopamine signalling in the brain plays an important modulatory role in a variety of motor and cognitive functions. We have identified region-specific functional abnormalities in dopaminergic function, which may help better account for the symptoms of ADHD.

Partial least squares regression (PLS) discriminant analysis distinguishes ADHD patients (red circles) from control subjects (black squares). Each object in the graph represents one individual. For each individual, the position in the plot is a compact representation of all regional Ki data collected. Objects that appear close to each other are generally similar across all variables. In this case, ADHD patients and controls form separate groups, reflecting underlying group differences in regional Ki values.

Regression coefficients in the PLS model discriminating ADHD patients vs. control subjects. A large positive coefficient indicates an increase in the corresponding variable in ADHD patients vs. controls. In this model, most coefficients are negative, reflecting a general decrease in Ki values in the ADHD group. In particular, subcortical Ki values (dark blue columns) tend to be negatively related to the ADHD diagnosis. See list of abbreviations to identify the anatomical ROIs

Regression coefficients in the PLS model relating attention score to regional Ki values in the ADHD group only. Large positive coefficients indicate a positive correlation, i.e., the larger the Ki, the higher the attention score. Large negative coefficients suggest an inverse relationship, where high Ki values are associated with low values in the attention score.